The efforts described in this proposal make use of neurophysiological and bioenergetic techniques to establish relationships between energy metabolism in the intact central nervous system and electrical activity of these tissues in cats. The effect on energy metabolism of pharmaceuticals and conditions such as changes in the oxygen level of the tissue are investigated with the goal of seeking new insights into the mechanisms of action of certain pharmaceutical agents and increasing knowledge of the role oxidative metabolism plays in normal and pathological conditions. Specifically, recent development of the microfluorometric monitoring technique to measure the oxidation-reduction level of intramitochondrial NADH has allowed a correlation between electrical and metabolic activity in a variety of intact preparations. The development of reflection spectrophotometry will permit monitoring of the redox state of cytachromes. The combination of these two techniques offers the opportunity to consider bioenergetic functioning at both the substrate and the oxygen end of the respiratory chain in intact, electrically normal central nervous system areas with undamaged blood supply. Pharmacological agents which have an effect at either end of the respiratory chain can be investigated. The role of oxygen in these tissues can be considered.